Important New MMRF-Led Study Reveals Previously Unknown Immune Features in Multiple Myeloma Patients with African Ancestry

First and largest study of its kind used MMRF data to uncover distinct immune features in this patient population.

The Black community bears a disproportionate burden of multiple myeloma in the U.S. Black individuals are twice as likely to be diagnosed with myeloma as other racial and ethnic groups and face the disease’s highest mortality rates.  These differences result from both systemic issues and poorly understood biology.

Black myeloma patients are less likely to receive high-dose chemotherapy and stem cell transplants, and they experience greater barriers to cutting-edge treatments like CAR T-cell therapy, despite the benefits of these therapies. Even though about 20 percent of all myeloma patients are Black, this group has historically made up just four percent of myeloma clinical trials.

But research has shown that when Black patients receive equal treatment as their white peers, they have equal or even superior survival outcomes. Some studies suggest that Black patients may have certain immune features to explain these differences, but overall, the field knows very little about how African ancestry relates to myeloma biology and the immune microenvironment.

Now, a new, first-of-its-kind study—published this week in the prestigious journal Blood from the Multiple Myeloma Research Foundation® (MMRF®), the Mayo Clinic, and Emory University—identifies several previously unrecognized immune features in patients with African ancestry.

“This study provides some of the strongest evidence to date that the immune environment surrounding myeloma differs in patients with African ancestry,” said MMRF Chief Scientific Officer George Mulligan, PhD, who was co-senior author of the study. “By uncovering previously unknown immune features, we’ve opened new avenues for further research into specific pathways that differ across myeloma patient populations. This sheds light on both population differences and the process of cancer emergence in all patients.”

This study set out to analyze patients with varying levels of African genetic similarity using genomic data instead of self-reported race data. Researchers examined how closely patients’ DNA aligned with African reference populations to identify those with high African genetic similarity. This more precise method helps researchers identify biological patterns that may not be apparent when people are only grouped by race, a social categorization that does not always reflect genetic ancestry.

Achieving that unprecedented level of detail required the unique combination of two critical MMRF datasets: The MMRF Immune Atlas provided a detailed view of the myeloma patient immune system, and the MMRF CoMMpass^SM Study provided the genomic and clinical data from these patients over time.

The MMRF Immune Atlas contains analyses of 1.4 million individual cells from patients with newly diagnosed myeloma, making it the most robust characterization of the myeloma immune microenvironment ever assembled. Researchers looked at bone marrow single-cell RNA sequencing data from 320 newly diagnosed patients in Immune Atlas to glean new insights about individual immune cells in patients with high African genetic similarity.

Researchers then layered in longitudinal genomic and clinical data from more than 1,000 patients in CoMMpass to estimate genetic similarity, analyze survival outcomes, and understand tumor genetics. Analyses of additional data from Mayo Clinic showed these findings are relevant more broadly.

“None of these datasets could have produced these findings on its own,” Mulligan said. “The Immune Atlas allowed us to examine individual immune cells in unprecedented detail, while CoMMpass provided the context needed to understand how those immune features relate to ancestry. Together, those resources enabled discoveries that would not have been possible just a few years ago.”

Researchers found that myeloma patients with high African genetic similarity had a distinct bone marrow immune microenvironment that was less inflammatory and contained more cancer-fighting immune cell types.

One of the researchers’ most striking findings was that patients with high African similarity were more likely to have a rare type of immune cell known as cytotoxic CD4+ T cells. CD4+ T cells are known as “helper cells” for their role coordinating immune response. In patients of African ancestry, however, researchers observed that their CD4+ T cells appear to take on direct cancer-fighting characteristics and were expressing genes associated with cytotoxicity (capable of killing cancer cells). The authors of the paper noted that this was a defining feature of the bone marrow immune microenvironment in these patients.

The study’s authors also observed that this group had more mature natural killer cells, another type of immune cell that helps the body eliminate cancer cells. They were also less likely to meet the IMS-IMWG definition of high-risk myeloma, though the authors noted that it’s not yet clear whether that’s because of biological differences or limitations in current risk models.

Understanding why myeloma behaves differently across different patient populations is essential to ensuring that all patients benefit from new and emerging treatments, and it sheds light on the biological processes that drive myeloma development and inform future breakthroughs. By mapping the immune microenvironment in patients with African ancestry, researchers and clinicians can begin exploring ways to improve risk assessment and optimize treatment for all myeloma patients.

“Many of our most effective myeloma treatments, including CAR T-cell therapies, bispecific antibodies and CD38-targeted antibodies, work through the immune system,” said co-senior author Manoj Bhasin, MS, PhD, cancer immunology researcher at Winship Cancer Institute and professor in the Department of Pediatrics at Emory University School of Medicine. “Understanding each patient’s immune environment may help us better match treatments to their biology. This is an important hypothesis that we now need to test.”

This study is among the first of a series of breakthrough publications from the MMRF Immune Atlas project, and it comes on the heels of another major study the MMRF and its collaborators published in Nature Cancer earlier this year. It also represents the MMRF’s continued commitment to open data sharing, collaboration, and health equity.

“To accelerate cures for every patient, our research resources must reflect the full diversity of the myeloma community,” said MMRF President and CEO Mike Andreini. “Studies like this underscore why equitable participation in research matters and how open, collaborative data platforms can help scientists uncover new insights.”